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Biomedical subjects

D Menache

Publications and source records attributed to D Menache.

At least 19 recordsLinked to original sources
PubMed1998

Pharmacokinetics of von Willebrand factor and factor VIII coagulant activity in patients with von Willebrand disease type 3 and type 2.

Nine patients with von Willebrand disease type 3, six with type 2B, one with type 2A, and one patient with type 1/2N were infused with one dose of approximately 50 or 100 IU ristocetin cofactor activity (RCoF) per kg body weight of von Willebrand factor (vWF) (Human), a product with a very low content of factor VIII (FVIII). Blood samples were collected over 96 h. The data for RCoF and vWF antigen (vWF:Ag) were fitted to a 1-compartment model decay. The data for FVIII:C were fitted to a model with a linear time 'synthesis' term and a 1-compartment decay. Results in von Willebrand disease type 3 patients (nine patients; 10 infusions) indicated a volume of distribution of 39.9 and 39.8 mL kg-1 for RCoF and vWF:Ag, respectively. The FVIII:C rate of synthesis was 6.4 U dL-1 h-1 (range: 4.4-8.8). The decay rates for FVIII:C, RCoF, and vWF:Ag were 0.041 (h-1) [t1/2: 16.9 h]; 0.061 (h-1) [t1/2: 11.3 h] and 0.006 (h-1) [t1/2: 12.4 h], respectively. In patients with von Willebrand disease type 2 (n = 8) the RCoF mean volume of distribution was 46 mL kg-1. The factor VIIIC mean rate of synthesis was 5.5 U dL-1 h-1 and the decay rate 0.043 (h-1) [t1/2: 16.1 h]. The rate of decay for RCoF and vWF:Ag were 0.050 (h-1) [t1/2: 13.9 h] and 0.044 (h-1) [t1/2: 15.7 h], respectively.

Factor VIII↗
PubMed1997

New treatments of von Willebrand disease: plasma derived von Willebrand factor concentrates.

During the past 10 years the quality of plasma derived virus inactivated products containing von Willebrand factor (vWF) has improved and the ratios of ristocetin cofactor activity (vWF:RCo) to von Willebrand factor antigen (vWF:Ag) have increased. There are, however, considerable variations in AHF-vWF products with ranges from 0.25 to 1.4 unit of vWF:RCo for each unit of vWF:Ag, and 0.5 to 5.3 units of vWF:RCo for each factor VIIIC (FVIIIC) unit. The availability of a vWF product depleted of FVIII has allowed pharmacokinetic studies of the vWF protein. There have been no dose response studies, dosage regimens remain empirical and are still, except in rare instances, based on FVIIIC dosage. Current concentrates are as effective as cryoprecipitate in the management of patients with vWD non responsive to DDAVP. These concentrates should be preferred to cryoprecipitate which carries a risk of virus transmission.

Antigens↗
PubMed1996

Creutzfeldt-Jakob disease: current U.S. policy to further reduce the possible risk of transmission by transfusion.

Because the results of epidemiological and subhuman primate studies conducted over the last quarter of a century have failed to show a statistically significant risk of transmission of CJD by transfusion of blood components or plasma derivatives, the FDA's position is that only a theoretical low risk of CJD transmission cannot be excluded at this time. Consequently, FDA issued two memoranda on 8 August 1995 as updated interim policy documents recommending: (1) permanent deferral from donating blood or plasma for all persons who state at the time of donation, or for whom post donation information becomes available, that they have ever received pit-hGh, a dura mater transplant graft, or have a blood relative history of CJD, unless this increased risk for CJD is excluded on the basis of genetic analysis testing; (2) the quarantining of all undistributed in-date units of blood or blood components collected from either of these three groups of donors together with notification of all consignees of such in-date units so that distributed units also can be quarantined and recipient tracing and notification may be effected, and (3) the withdrawal from distribution and quarantining of in-date plasma derivative products derived from plasma pools containing a unit from either of these three groups of donors at known high risk for CJD, or donors subsequently diagnosed as having CJD. Consignees of these products are to be notified in order that they, in turn, may inform physicians or other qualified personnel responsible for the care of product recipients to provide counseling as deemed medically appropriate. The 'family history of CJD' criterion was further clarified to mean a 'history of CJD in 2 or more family members' during the BPAC meeting of 14 December 1995. In a workshop meeting on 29 January 1996 the FDA urged that additional laboratory animal data be generated by plasma derivative manufacturers in order to ascertain if the sterilization steps used in their production of plasma derivatives further reduce the risk of transmission of CJD.

Blood Transfusion↗
PubMed1996

Pharmacokinetics of von Willebrand factor and factor VIIIC in patients with severe von Willebrand disease (type 3 VWD): estimation of the rate of factor VIIIC synthesis. Cooperative Study Groups.

Nine patients (10 infusions) with a confirmed diagnosis of type 3 VWD were infused with von Willebrand factor (human), a preparation of von Willebrand factor (VWF) with a very low factor VIII content. Each patient was infused with one dose of approximately 50 or 100 iu ristocetin cofactor activity (VWF:RiCoF) per kg body weight. Bleeding times were performed during the 24 h period after infusion. Plasma samples were obtained over the 96 h period after infusion and were analysed for factor VIII coagulant activity (FVIIIC), VWF:RiCoF, von Willebrand factor antigen (VWF:Ag), and multimers. The FVIIIC data were analysed by non-linear least-squares analysis assuming constant FVIIIC 'synthesis' and exponential decay. The VWF data were fitted for exponential decay. The average decay rates for FVIIIC, VWF:RiCoF and VWF:Ag were 0.041, 0.061 and 0.056 respectively. The average calculated 'synthesis' rate for FVIIIC was 6.4 u/dl/h. The synthesis of FVIIIC was slightly faster and the decay slightly slower following the infusion of 100 iu VWF:RiCoF/kg than of 50 iu VWF:RiCoF/kg. Correction of the bleeding time was strongly dose dependent. At 4 h post infusion the median bleeding time was 9 min following a dose of 50 iu VWF:RiCoF/kg versus 3 min with a dose of 100 iu VWF:RiCoF/kg. There was no decrease in the bleeding time until the level of VWF:Ag or VWF:RiCoF reached > 100 u/dl.

Adolescent↗
PubMed1995

Safety monitoring and epidemiological surveillance of blood transfusion in the United States.

Safety monitoring and epidemiological surveillance of blood transfusion in the United States is complex and involves government agencies and independent organizations. Several systems of control are in place nationwide to ensure that blood, blood components, and plasma derivatives meet prescribed standards. Control and surveillance of drugs that are biologics, which include human blood, blood components and plasma derivatives, are exercised by the Food and Drug Administration. Epidemiological surveillance involves several agencies and organizations that constitute a network capable of rapidly detecting unusual adverse events.

Biological Products↗
PubMed1992

Antithrombin III concentrates.

The general characteristics of antithrombin III (AT III) concentrates available in the United States are described in this article. The effectiveness of AT III concentrates in the prevention and treatment of thrombotic episodes in patients with hereditary AT III deficiency are summarized, and the use of this product in various conditions with acquired AT III deficiency are reported.

Antithrombin III↗
PubMed1990

Evaluation of the safety, recovery, half-life, and clinical efficacy of antithrombin III (human) in patients with hereditary antithrombin III deficiency. Cooperative Study Group.

Antithrombin III (Human) (AT III) was administered to 18 patients with documented hereditary AT III deficiency. In eight patients with no ongoing clinical symptoms of thrombosis, the percent increase per unit AT III infused per kilogram of body weight ranged from 1.56% to 2.74%, and the half-life from 43.3 to 77.0 hours. No significant difference was noted between patients receiving and those not receiving coumarin therapy. In clinically ill patients, the in vivo recovery was significantly lower and ranged from 0.64% to 1.90% increase per unit AT III infused/kg. Efficacy of AT III was evaluated in 13 patients for the prevention or treatment of thrombosis. AT III was efficacious as assessed by the absence of thrombotic complications after surgery and/or parturition, and the nonextension and nonrecurrence of thrombosis in patients exhibiting an acute thrombotic episode. No side effects were noted. Follow-up studies indicated no hepatitis B seroconversion and no alanine aminotransferase elevations in patients who were not transfused with other blood products.

Adult↗
PubMed1987

Thrombogenicity of factor IX complex: in vivo investigation.

Factor IX Complex therapy has been associated with thrombosis when used in patients with liver disease, hemophilia B and hemophilia A with inhibitors to Factor VIII when administered repetitively and in high doses. Three mechanisms for inducing thrombogenicity have been proposed: activated coagulants, coagulant-active phospholipid content and/or the high zymogen level attained in recipients. A new animal model using Russel Viper Venom (RVV) as an in vivo stimulus of coagulation has been used to investigate the role of high levels of zymogens in the induction of thrombosis. The quantity of RVV tolerated by rabbits infused with Factor IX Complex is reduced 100-fold. Infusion of Factor X or prothrombin also reduces the lethal dose of RVV. In contrast, Coagulation Factor IX devoid of other coagulants has little effect. However other animal data indicate that the amount of activated coagulants can play a role in the in vivo thrombogenicity of Factor IX Complex.

Animals↗
PubMed1985

Measures to inactivate viral contaminants of pooled plasma products.

In order to produce safer plasma products all possible methods of virus inactivation and reduction must be investigated systematically. Since the number and types of viruses are unknown and could change with time, a general viricidal approach is necessary. While heating has been the standard, a variety of methods are available for reducing the transmission of virus infection by blood products. Satisfactory development of these methods is limited by the cumbersome, expensive and imprecise experimental tools being used, i.e., the chimpanzee or human clinical trials.

Animals↗
PubMed1984

Coagulation Factor IX concentrate: method of preparation and assessment of potential in vivo thrombogenicity in animal models.

Thrombosis and/or disseminated intravascular coagulation (DIC) are complications specifically associated with the use of factor IX complex in some patients. Assuming that these complications might result from zymogen overload, we have produced, using diethylaminoethyl (DEAE)-Sephadex (Pharmacia, Piscataway, NJ) and sulfated dextran chromatography, a factor IX concentrate (coagulation factor IX) that is essentially free of prothrombin, factor VII, and factor X. Factor IX specific activity is at least 5 U/mg protein, a 250-fold purification compared to plasma. Amounts of factors II, VII, and X are less than 5 units each per 100 units of factor IX. The concentrate is essentially free of activated clotting factors and contains no added heparin. In the rabbit stasis model, a dose of 200 factor IX U/kg was less thrombogenic than 100 factor IX U/kg of the DEAE-Sephadex eluate from which the concentrate was derived. Infusion of 200 factor IX U/kg did not induce DIC in the nonstasis rabbit model, whereas 100 factor IX U/kg of the DEAE-Sephadex eluate resulted in DIC in this model. Several factor IX lots were found to have shortened nonactivated partial thromboplastin times (PTTs), but were nonthrombogenic in both animal models. These data indicate that coagulation factor IX concentrate is less thrombogenic than factor IX complex.

Animals↗
PubMed1982

Rapid methods for isolation of human plasma fibronectin.

Simplified procedures have been developed for isolation of human plasma fibronectin by affinity chromatography on gelatin-agarose. In one method, fibronectin is eluted with 3 M urea, and this reagent is quickly removed by adsorbing the protein onto heparin-agarose, followed by 0.4 M NaCl elution. In a shorter process, fibronectin is eluted from gelatin-agarose simply by decreasing the buffer pH below 6. After lyophilization the purified protein can be readily dissolved in water. The fraction not adsorbed to gelatin can be used to purify other proteins, including factor VIII whose procoagulant activity is quantitatively recovered.

Chemical Precipitation↗